Plasmon Resonance Research Articles

Picometer Scale Photothermal Tuning of Plasmonic Nanocavities and Interfacial Processes.

The ability to precisely tune plasmon resonances is critical for advancing nanophotonic and sensing technologies. In this work, we exploit the photothermal effect to achieve picometer-level tunability of plasmon resonances in nanorod-on-mirror nanocavities, using polyelectrolyte (PE) layers as dielectric spacers. The plasmon-induced thermal response of these soft materials allows real-time adjustment of the nanocavity, unlike stable inorganic spacers like aluminum oxide. Under continuous laser illumination, the PE spacers undergo thickness reduction and phase transitions, leading to significant shifts in plasmon resonances. These shifts are influenced by laser power and initial spacer thickness, which govern near-field enhancement and photothermal effects. It is shown that this precise tuning capability enables the exploration of various photophysical processes, including the excitation of higher-order plasmon modes, optomechanical enhancement of surface-enhanced Raman scattering signals, electron tunneling, molecular diffusion from the nanocavities, and the transition to charge transfer plasmons.

Nonclinical Similarity of the Biosimilar Candidate ABP 938 with Aflibercept Reference Product.

ABP 938 is being developed as a biosimilar to Eylea® (aflibercept reference product [RP]), an anti-vascular endothelial growth factor (VEGF) drug used in the management of retinal diseases. Previously, a comparative analytical similarity assessment demonstrated that ABP 938 and aflibercept RP have the same amino acid sequence and exhibit similar higher-order structure and biological activity. The nonclinical studies described here were designed to assess the in vitro pharmacology and the in vivo pharmacokinetics (PK), toxicokinetics (TK), and safety profiles of ABP 938 compared to aflibercept RP. In vitro target-binding kinetics and affinity for VEGF-A and placental growth factor (PIGF) isoforms were evaluated using surface plasmon resonance (SPR). Effector functions were assessed by cell-based assays. PK was evaluated in a nonterminal intravitreal (IVT) ocular distribution study in rabbits. Safety was assessed in a 1-month IVT study in cynomolgus monkeys. SPR results demonstrated that ABP 938 is similar to aflibercept RP in binding kinetics and affinity for VEGF-A111, VEGF-A121, VEGF-A165, VEGF-A189, PlGF-1, and PlGF-2 isoforms. No antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, or complement-dependent cytotoxicity was observed with ABP 938 and aflibercept RP. Results from thenonterminal ocular distribution study in rabbits indicated that there were no meaningful differences in the distribution kinetics between intravitreally injected ABP 938 and aflibercept RP. Additionally, there was no evidence of ocular or systemic toxicity associated with IVT administration of ABP 938 in a repeat-dose, 1-month toxicology study in cynomolgus monkeys; toxicokinetic and toxicology profiles were similar to aflibercept RP. This integrated assessment of results from the in vitro pharmacology assessment and in vivo PK and TK/toxicology profiles formed the nonclinical portion of the totality of evidence demonstrating ABP938 is a biosimilar to aflibercept RP.

Lysosomal enzyme binding to the cation-independent mannose 6-phosphate receptor is regulated allosterically by insulin-like growth factor 2.

The cation-independent mannose 6-phosphate receptor (CI-MPR) is clinically significant in the treatment of patients with lysosomal storage diseases because it functions in the biogenesis of lysosomes by transporting mannose 6-phosphate (M6P)-containing lysosomal enzymes to endosomal compartments. CI-MPR is multifunctional and modulates embryonic growth and fetal size by downregulating circulating levels of the peptide hormone insulin-like growth factor 2 (IGF2). The extracellular region of CI-MPR comprises 15 homologous domains with binding sites for M6P-containing ligands located in domains 3, 5, 9, and 15, whereas IGF2 interacts with residues in domain 11. How a particular ligand affects the receptor's conformation or its ability to bind other ligands remains poorly understood. To address these questions, we purified a soluble form of the receptor from newborn calf serum, carried out glycoproteomics to define the N-glycans at its 19 potential glycosylation sites, probed its ability to bind lysosomal enzymes in the presence and absence of IGF2 using surface plasmon resonance, and assessed its conformation in the presence and absence of IGF2 by negative-staining electron microscopy and hydroxyl radical protein footprinting studies. Together, our findings support the hypothesis that IGF2 acts as an allosteric inhibitor of lysosomal enzyme binding by inducing global conformational changes of CI-MPR.

Biosynthesis of Gold Nanoparticles Using Sambiloto Leaf Extracts and its Characteristics

Gold nanoparticles (AuNPs) have been successfully synthesized using aqueous sambiloto (Andrographis Paniculata Ness) leaf extract as a reducing agent. This method of synthesizing nanoparticles is called biosynthesis. Characterization was carried out using various techniques including UV-Vis, FTIR, and TEM. The results showed that the optimal synthesis ratio, i.e., AuCl3 solution : sambiloto leaf extract, was 30 µl : 10 ml with a synthesis rate of 0.159 a.u./h. The characteristic of the gold nanoparticles synthesized is that the surface Plasmon resonance (SPR) wavelength is 529.00 nm; it was stable after 4 hours of synthesis and stayed until 24 hours at an SPR wavelength of 527.00-531.50 nm. The functional groups formed include O-H, aliphatic C-H, C=O stretch, aromatic C=C stretch, and C-O stretch. The size of the nanoparticles is in the range of 1-20 nm.

In Situ and Label-Free Quantification of Membrane Protein–Ligand Interactions Using Optical Imaging Techniques: A Review

Membrane proteins are crucial for various cellular processes and are key targets in pharmacological research. Their interactions with ligands are essential for elucidating cellular mechanisms and advancing drug development. To study these interactions without altering their functional properties in native environments, several advanced optical imaging methods have been developed for in situ and label-free quantification. This review focuses on recent optical imaging techniques such as surface plasmon resonance imaging (SPRi), surface plasmon resonance microscopy (SPRM), edge tracking approaches, and surface light scattering microscopy (SLSM). We explore the operational principles, recent advancements, and the scope of application of these methods. Additionally, we address the current challenges and explore the future potential of these innovative optical imaging strategies in deepening our understanding of biomolecular interactions and facilitating the discovery of new therapeutic agents.

Surface Plasmon Modulation in Cu3-xP Nanocrystals.

We demonstrate modulation of the surface plasmon resonance in nonstoichiometric copper phosphide nanocrystals using spectroelectrochemical methods. Application of an anodic potential resulted in a blue-shift of the surface plasmon resonance and an incremental increase in its extinction coefficient. Conversely, upon application of a cathodic potential, the surface plasmon band red-shifted and reduced in intensity. These changes were found to be reversible over multiple cycles of anodic and cathodic potential steps. We also discuss how the postsynthetic ligand treatment impacts the surface plasmon peak and the structure of Cu3-xP nanocrystals. For example, the addition of alkylthiols resulted in the chemical decomposition of the nanocrystals. This work demonstrates how the surface plasmon peak in Cu3-xP can be used to probe changes in the structure and carrier density in these nanocrystals.

Core–Shell–Satellite Au@CeO2–Pd Plasmonical Photocatalysts for Suzuki–Miyaura Coupling Reaction

ABSTRACTIntegration of localized surface plasmon resonance (LSPR) metallic nanocrystals into photocatalysis is an intriguing approach for light‐driven organic transformations. However, uncertain direction of hot carriers is a grand challenge, which fails to take full advantage of the LSPR excitation. In this work, core–shell gold@ceria nanosphere–supported segregated palladium species (Au@CeO2–Pd) have developed to steer the light absorption capability and charge carrier migration. Under simulated solar light irradiation, the core–shell–satellite Au@CeO2–Pd exhibited efficient light harvesting and colossal activity in the Suzuki coupling reaction. The plasmon‐induced hot electrons overpassed the Schottky barrier at the Au@CeO2 interfaces and migrated from Au core to CeO2 shell accordingly. Subsequently, the photogenerated electrons and hot electrons migrated from Au@CeO2 core–shells to Pd, which acted as an electron acceptor. Detailed photocatalytic mechanism studies revealed that both photoexcited electrons and holes were the main active species involved in the photocatalytic Suzuki coupling reaction process. In particular, the diphenyl yield over Au@CeO2–Pd catalyst was ~1.7 times higher than that of core–shell–satellite Au@SiO2–Pd, where a 19‐nm‐thick SiO2 shell was introduced to prevent the migration of hot electrons. This distinctly certified that the hot electrons transfer in the core–shell–satellite Au@CeO2–Pd under illumination played an important role to drive Suzuki reaction. Overall, this design of core–shell–satellite Au@CeO2–Pd plasmonic photocatalyst has the potential in the field of photo‐driven organic transformations.

Application of surface Plasmon resonance imaging in the high-throughput detection of influenza virus.

To evaluate the application effect of SPRi monoclonal antibody (mAb) chip in the detection of influenza virus antigen in complex mixtures. A total of 115 strains of mAbs against different subtypes (H1N1, H5N1, A1, A3, B, H7N9, H9N2, and H3N2) of influenza virus were prepared. The chip of mAbs against influenza virus was prepared by surface plasmonic resonance imaging (SPRi) technology, which was used for the detection of influenza virus supernatant, and compared with the traditional antigen capture ELISA method. Comparative studies have shown that traditional antigen capture ELISA methods have a higher sensitivity (86.8% (46/53) vs. 46.5% (46/99); z = 4.84, P < .001), while the SPRi chip methods present a significantly higher specificity (56.3% (9/16) vs. 14.5% (9/62); z = 3.54, P < .001). The SPRi chip detection method for influenza virus antibodies can well reflect the specific binding characteristics of influenza virus antigens and antibodies. The SPRi mAb chip can be used for the detection of specific pathogenic microorganisms or viral proteins in complex mixtures such as influenza virus supernatant. It has significant advantages of label free, real-time, high-throughput, and good specificity, and can play an important role in disease diagnosis and infectious disease prevention and control.

Helicoid Grating-Coupled Surface Plasmon Resonance Sensor.

Ultrasensitive, rapid, and reliable biomolecular sensing is essential for biomedical diagnostics, requiring real-time monitoring and detection of trace samples. Optical sensing, particularly plasmonic biosensing, meets these demands through noninvasive, high-sensitivity detection based on the interaction between light and molecules. Here, we present novel plasmonic metamaterial-based sensing strategy, utilizing the circular dichroism (CD) response of grating-coupled surface plasmon resonance (SPR) from chiral nanoparticle grating structure (i.e., 2D helicoid crystal) on gold substrate. Strong chiroptic response of helicoids has been effectively expanded to produce a remarkable CD/greflection response in the SPR mode, achieved by spectral coupling of SPR with localized surface plasmon resonance (LSPR) in helicoids. This CD response, derived from the differential of left and right circularly polarized light, corrects optical fluctuations, enhancing sensitivity and reliability. Our SPR-CD-based approach achieves a sensitivity of 379.2 nm/RIU and detection limit of a few mM for d-glucose, offering a new paradigm for high-performance optical biosensors.

AuNPs enhanced electrochemical and optical dual-mode fiber optic sensor for trace Hg2+ detection

Efficient and low-concentration detection of heavy metal ions is crucial for healthcare and environmental monitoring. Traditional fiber optic surface plasmon resonance (SPR) sensors face challenges in detecting trace heavy metal ions due to limited sensitivity and the need for complex specific modifications. To overcome these challenges, an innovative electrochemical and optical dual-mode fiber optic sensor for in situ, real-time detection of trace mercury ions is proposed in this paper. The sensor utilizes a reflection-type fiber optic probe coated with thin gold (Au)/indium tin oxide (ITO) film and gold nanoparticles (AuNPs), enabling simultaneous electrochemical and optical interrogation. The coupling effect between the SPR of thin film and the localized surface plasmon resonance (LSPR) of AuNPs significantly improves optical sensitivity, with AuNPs also offering additional active sites for the redox reaction of Hg2+. The ITO film not only facilitates the stripping of Hg2+, leading to sharper stripping peaks but also enhances the ability of the sensor to rapidly respond to anomalous potential changes. Experimental results show that the sensor has a wide dynamic detection range from 10−10 M to 10−5 M, with a limit of detection reaching the pM level. The dual-mode functionality allows the simultaneous collection of voltage, current, and optical information, enabling cross-validation of the detection results and improving the accuracy and reliability of detection.

Eccentric Core Photonic Crystal Fiber Magnetic Field Sensor Based on Surface Plasmon Resonance with Extremely High Linearity

Eccentric Core Photonic Crystal Fiber Magnetic Field Sensor Based on Surface Plasmon Resonance with Extremely High Linearity

A Facile Microwave-Promoted Formation of Highly Photoresponsive Au-Decorated TiO2 Nanorods for the Enhanced Photo-Degradation of Methylene Blue

The integration of noble metal nanoparticles (NPs) effectively modifies the electronic properties of semiconductor photocatalysts, leading to improved charge separation and enhanced photocatalytic performance. TiO2 nanorods decorated with Au NPs were successfully synthesized using a cost-effective, rapid microwave-assisted method in H2O2 and HF media for methylene blue (MB) degradation under visible light illumination. X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), N2 physisorption, and UV–vis spectroscopy were employed to characterize the structures, morphologies, compositions, and photoelectronic properties of the as-synthesized materials. The fusing of Au NPs effectively alters the electronic structure of TiO2, enhancing the charge separation efficiency and improved electrical conductivity. The HF treatment promotes the exposure of the highly reactive (001) and (101) crystalline facets. The improved photocatalytic activity of Au/TiO2, achieving 97% efficiency, is attributed to the surface plasmon resonance (SPR) effect of the Au NPs and the presence of oxygen vacancies. The photodegradation of MB using the TiO2/Au photocatalysts follows pseudo-first-order kinetics, highlighting the enhanced catalytic efficiency of the synthesized nanostructures. The exceptional properties of the binary Au/TiO2 photocatalysts, including the SPR effect, exposed crystallographic faces, and efficient charge carrier separation through a decrease in the recombination of electrons and holes, contribute to the photocatalytic degradation of MB.

Unique features of plasmonic absorption in ultrafine metal nanoparticles: unity and rivalry of volumetric compression and spill-out effect

Abstract We present a solution to a longstanding challenge in nanoplasmonics and colloid chemistry: the anomalous optical absorption of noble metal nanoparticles in the ultrafine size range of 2.5–10 nm, characterized by a rapid long-wavelength shift in plasmon resonance as the particle size increases. Our investigation delves into the impact of alterations in electron density along the radial direction of nanoparticles and the resulting variations in dielectric constants on the spectral positioning of the plasmon resonance. We explore the interplay of the spill-out effect, volumetric compression, and their combined impact in different experimental conditions on electron density variation within the particle volume and its blurring at the particle boundary. The latter effectively forms a surface layer with altered dielectric constants and a size-independent extent. As particle size decreases, the influence of the surface layer becomes more pronounced, especially when its extent is comparable to the particle radius. These findings are specific to ultrafine plasmonic nanoparticles and highlight their unique properties.

High performance SERS boosting by Fabry- Pérot cavities of silica-gold-silicon multilayers

Surface-enhanced Raman scattering (SERS), an advanced technique for molecular spectroscopy, relies heavily on the preparation of SERS active materials that can significantly enhance the Raman scattering signals for highly sensitive detection of trace molecules. Traditionally, SERS measurements are performed on silicon or silica substrates, the SERS performance is determined by the structure of SERS materials. Here, we show that the SERS signal can be amplified and modulated using Fabry-Pérot (F-P) cavities made of silica-silicon (SiO2-Si) or silica-gold-silicon (SiO2-Au-Si) multilayers as substrates. Periodic SERS signal variations as SiO2 thickness increases are observed, exhibiting optimal enhancement with the SiO2 thickness of 250 nm due to the optical interference in the cavity. Although the signal enhancement by optical interference is weaker than that by plasmonic resonance, additional signal amplification is essential for highly sensitive SERS materials. Moreover, we applied this strategy to detect thiram in bean sprout extracts, demonstrating that the detection sensitivity is two orders of magnitude higher than that using Si substrates. The utilization of the pseudo-internal standard intensity calibration method facilitates the quantitative analysis of thiram concentrations. Our results provide a promising approach for further amplification of SERS signals with great potential for practical applications.

Compatibility and antimicrobial activity of silver nanoparticles synthesized using Lycopersicon esculentum peels.

Nanoparticles have gained worldwide attention as a new alternative to chemical control agents due to their special physiochemical properties. The current study focused on the environmentally friendly synthesis of silver nanoparticles (AgNPs) using Lycopersicon esculentum peel. In addition to studying the intrinsic cytotoxic effectiveness of Le-AgNPs contribute to their antibacterial, and antifungal activities and the effect of nanoparticles on the integrity of their morphological behavior. The initiative biosynthesis of L. esculentum silver nanoparticles (Le-AgNPs) was indicated by the color change of L. esculentum (Le) extract mixed with silver nitrate (AgNO3) solution from faint pink to faint brown. UV-visible spectroscopy, Dynamic light scattering (DLS), Fourier-transform infrared spectroscopy, high-resolution transmission electron microscopy (HR-TEM), and X-ray diffraction techniques were used to characterize biosynthesized Le-AgNPs. Results of UV-visible spectroscopy recorded surface plasmon resonance at 310nm for SPR of 2.5. The DLS results showed particles of 186nm with a polydispersity index of 0.573. The FTIR spectrum indicated the existence of carboxyl, hydroxyl, phenolic, and amide functional groups. The HR-TEM analysis revealed quasi-spherical crystal particles of Le-AgNPs. Le-AgNPs had a negative zeta potential of - 68.44mV, indicating high stability. Bacillus subtilis ATCC 6633 and Escherichia coli ATCC 8739 were the most susceptible pathogens to Le-AgNPs inhibition, with inhibition zone diameters (IZDs) of 4.0 and 0.92cm, respectively. However, Listeria monocytogenes NC 013768 and Shigella sonnei DSM 5570 were the most resistant pathogens, with IZDs of 0.92 and 0.90cm, respectively. Le-AgNPs demonstrated good inhibitory potential against pathogenic fungi, with IZDs of 3.0 and 0.92cm against Alternaria solani ATCC 62102 and Candida albicans DSM 1386, respectively. The cytotoxicity effect was observed at a half-maximal inhibitory concentration (IC50) of 200.53μg/ml on human colon NCM460D normal cells.

Is Osteopontin a Reliable Biomarker for Endometriosis?

This study aimed to evaluate the concentration of osteopontin in peritoneal fluid and plasma as potential biomarkers for diagnosing endometriosis. Osteopontin levels were measured using surface plasmon resonance imaging (SPRI) biosensors in patients suspected of having endometriosis. Plasma samples were collected from 120 patients, and peritoneal fluid was collected from 86 patients. Based on the detection of endometriosis lesions during laparoscopy, participants were divided into a study group (patients with endometriosis) and a control group (patients without endometriosis). The results showed no significant differences in plasma osteopontin levels between women with endometriosis and the control group (19.86 ± 6.72 ng/mL vs. 18.39 ± 4.46 ng/mL, p = 0.15). Similarly, peritoneal fluid osteopontin concentrations did not differ significantly between patients with and without endometriosis (19.04 ± 5.37 ng/mL vs. 17.87 ± 5.13 ng/mL, p = 0.29). Furthermore, osteopontin levels in both plasma and peritoneal fluid were not significantly associated with the stage of endometriosis, the presence of endometrioma, or the menstrual cycle phase. The findings of this study do not support osteopontin concentration as a reliable biomarker for endometriosis. However, further research is necessary to explore osteopontin’s potential role in the disease.

Improved Rapid Equilibrium Dialysis-Mass Spectrometry (RED-MS) Method for Measuring Small Molecule-Protein Complex Binding Affinities in Solution.

Rapid equilibrium dialysis (RED) is predominantly used for the characterization of drug absorption, distribution, metabolism, and excretion (ADME) properties in plasma and biological fluids. We describe herein improvements in the use of RED in conjunction with mass spectrometry (RED-MS) to enable robust binding affinity measurements of small molecules for recombinant proteins and complexes from a single dialysis data set. The affinities calculated from RED-MS correlated well with measurements by both surface plasmon resonance (SPR) and affinity selection mass spectrometry (AS-MS). The method was particularly useful for quantifying the binding of small molecules to large protein complexes that were not amendable by common biophysical characterization techniques. Compound pooling and integration with automated liquid handling increased assay throughput and enabled the analysis of hundreds of measurements per week. RED-MS offers a viable option for measuring compound binding in solution and may facilitate small molecule affinity optimization toward difficult-to-drug protein complexes.

Developments in Localized Surface Plasmon Resonance

AbstractLocalized surface plasmon resonance (LSPR) is a nanoscale phenomenon associated with noble metal nanostructures that has long been studied and has gained considerable interest in recent years. These resonances produce sharp spectral absorption and scattering peaks, along with strong electromagnetic near-field enhancements. Over the past decade, advancements in the fabrication of noble metal nanostructures have propelled significant developments in various scientific and technological aspects of LSPR. One notable application is the detection of molecular interactions near the nanoparticle surface, observable through shifts in the LSPR spectral peak. This document provides an overview of this sensing strategy. Given the broad and expanding scope of this topic, it is impossible to cover every aspect comprehensively in this review. However, we aim to outline major research efforts within the field and review a diverse array of relevant literature. We will provide a detailed summary of the physical principles underlying LSPR sensing and address some existing inconsistencies in the nomenclature used. Our discussion will primarily focus on LSPR sensors that employ metal nanoparticles, rather than on those utilizing extended, fabricated structures. We will concentrate on sensors where LSPR acts as the primary mode of signal transduction, excluding hybrid strategies like those combining LSPR with fluorescence. Additionally, our examination of biological LSPR sensors will largely pertain to label-free detection methods, rather than those that use metal nanoparticles as labels or as means to enhance the efficacy of a label. In the subsequent section of this review, we delve into the analytical theory underpinning LSPR, exploring its physical origins and its dependency on the material properties of noble metals and the surrounding refractive index. We will discuss the behavior of both spherical and spheroidal particles and elaborate on how the LSPR response varies with particle aspect ratio. Further, we detail the fundamentals of nanoparticle-based LSPR sensing. This includes an exploration of single-particle and ensemble measurements and a comparative analysis of scattering, absorption, and extinction phenomena. The discussion will extend to how these principles are applied in practical sensing scenarios, highlighting the key experimental approaches and measurement techniques.

Low-energy (0–9 eV) electron interaction with gas phase 1,3-dichlorobenzene: an experimental and theoretical study

Abstract Dichlorobenzene used widely in industry for the synthesis of complex products, such as polymers. The processes using this compound require, as the initial step, the breakage of the C–Cl bond. In this work, we study the interaction of electrons with 1,3 dichlorobenzene molecules not only below 2 eV [M Mahmoodi-Darian et al 2001 J. Phys. Chem. A 113 11923–14929] but also at higher energies, i.e., up to 10 eV. In this investigated energy range, the electron induces the cleavage of the C–Cl bond producing essentially a Cl− anion and the chlorobenzene radical via dissociative electron attachment. The experimental measurements are completed with quantum scattering treatments providing the resonant states and also the integral scattering cross sections. These outcomes may potentially contribute to elaborate synthesis strategies using electrons (i.e., cold plasma, surface plasmon resonance, …).

Critical role of ROCK1 in AD pathogenesis via controlling lysosomal biogenesis and acidification

BackgroundLysosomal homeostasis and functions are essential for the survival of neural cells. Impaired lysosomal biogenesis and acidification in Alzheimer’s disease (AD) pathogenesis leads to proteolytic dysfunction and neurodegeneration. However, the key regulatory factors and mechanisms of lysosomal homeostasis in AD remain poorly understood.MethodsROCK1 expression and its co-localization with LAMP1 and SQSTM1/p62 were detected in post-mortem brains of healthy controls and AD patients. Lysosome-related fluorescence probe staining, transmission electron microscopy and immunoblotting were performed to evaluate the role of ROCK1 in lysosomal biogenesis and acidification in various neural cell types. The interaction between ROCK1 and TFEB was confirmed by surface plasmon resonance and in situ proximity ligation assay (PLA). Moreover, we performed AAV-mediated ROCK1 downregulation followed by immunofluorescence, enzyme-linked immunosorbent assay (ELISA) and behavioral tests to unveil the effects of the ROCK1–TFEB axis on lysosomes in APP/PS1 transgenic mice.ResultsROCK1 level was significantly increased in the brains of AD individuals, and was positively correlated with lysosomal markers and Aβ. Lysosomal proteolysis was largely impaired by the high abundance of ROCK1, while ROCK1 knockdown mitigated the lysosomal dysfunction in neurons and microglia. Moreover, we verified ROCK1 as a previously unknown upstream kinase of TFEB independent of m-TOR or GSK-3β. ROCK1 elevation resulted in abundant extracellular Aβ deposition which in turn bound to Aβ receptors and activated RhoA/ROCK1, thus forming a vicious circle of AD pathogenesis. Genetically downregulating ROCK1 lowered its interference with TFEB, promoted TFEB nuclear distribution, lysosomal biogenesis and lysosome-mediated Aβ clearance, and eventually prevented pathological traits and cognitive deficits in APP/PS1 mice.ConclusionIn summary, our results provide a mechanistic insight into the critical role of ROCK1 in lysosomal regulation and Aβ clearance in AD by acting as a novel upstream serine kinase of TFEB.